Immunocytochemical and Pharmacological Characterisation of P2-purinoceptor-mediated Cell Growth and Death in PC-3 Hormone Refractory Prostate Cancer Cells

  1. GEOFFREY BURNSTOCK5
  1. 1Bedford Hospital Department of Urology, Royal Free Hospital, London
  2. 2Urology Research Registrar, Royal Free Hospital, London
  3. 3Department of Clinical Biochemistry, Royal Free and University College Medical School (Royal Free Campus), University College London
  4. 4Department of Urology, Royal Free and University College Medical School (Royal Free Campus), University College London
  5. 5Department of Anatomy and Autonomic Neuroscience Institute, Royal Free and University College Medical School (Royal Free Campus), University College London, U.K.
  1. Correspondence to: M. Shabbir, Department of Urology, Royal Free Hospital, Pond Street, London NW3 2QG, U.K. Tel: 0044 7989 419635, e-mail: majidshabbir{at}hotmail.com

Abstract

Background: Extracellular nucleotides (e.g. adenosine 5’-triphosphate, ATP) influence biological processes via purinergic receptors. We characterised the P2-purinoreceptors in human hormone refractory prostate cancer (HRPC) cells (PC-3 cells). Results: 1. Immunofluorescent staining demonstrated P2X3, P2X4, P2X5, P2X7 and P2Y2 receptors. 2. ATP inhibited cell growth by up to 91% over 72h. Pharmacological characterisation indicated a P2X-purinoreceptor-mediated response. 3. Comparable maximum growth inhibition was seen after either a single addition of 1mM or daily addition of 100mM ATP. ATP concentrations ([ATP]) returned to baseline levels within 24h if the initial [ATP] was ≤100 μM, while [ATP] remained high for 72h if a single concentration of 1 mM was used. 4. ATP 1 mM significantly (p<0.001) increased the proportion of cells undergoing apoptosis from 0.27% (± 0.04%) to 5.28% (± 0.77%). Conclusion: Threshold concentrations of ATP inhibited HRPC cell growth in vitro via the activation of P2X-purinoreceptors. The role of nucleotides in the treatment of HRPC requires further investigation.

Footnotes

  • * Both R.C. Calvert and M. Shabbir made an equal contribution to the experimental and written aspects of this study.

    • Received July 21, 2004.
    • Accepted July 30, 2004.
| Table of Contents
www.farm-pump-ua.com

вимакс капсулы купить киев

www.eurobud.com.ua